Large cell lymphoma and lymphosarcoma are a group of malignant cancers of the lymphoid tissue that form solid primary and metastatic masses. The murine cell line RAW117 closely parallels highly malignant, human large cell lymphoma in cell type, disease course, tumor distribution, and organ involvement. We have developed metastatic variant cell lines of RAW117 by sequential in vivo as well as in vitro selection methods to obtain stable tumor cell variant lines of differing metastatic potentials and organ colonization preferences. The cell surface components of these variant cell lines have been examined and compared to parental cells for biochemical, immunological, and enzymatic changes to determine which cell surface components are important in malignancy and metastasis to particular sites in vivo. We have found that cell surface changes in the RNA tumor virus envelope glycoprotein gp70 (decrease) and another glycoprotein gp150 (increase) may account for differences in liver colonization. In this case, loss of gp70 results in a decrease in ability of the tumor cells to be recognized and killed by host immune systems, and an increase in gp150, which appears to be similar to a fetal liver adhesion antigen, results in increased liver colonization abilities and accounts for the differences in immunological and biological properties of the RAW117 cells. RAW117 cells are killed and/or growth-inhibited by macrophages, and the most malignant cells are much less sensitive to macrophage-mediated killing and/or growth inhibition. Evidence for the involvement of the embryonic antigen in liver homing was shown in experiments where liver colonization was abolished by pretreatment with Fab antibodies made against embryonic liver cell adhesion molecules. Thus, it appears that metastasis is controlled by the ability of lymphoma cells to invade host immune mechanisms and their ability to utilize normal embryonic recognition systems for distant organ colonization. (A)